Metabolic syndrome (Metsyn) is a condition of coexisting abnormalities in glucose, lipid, blood pressure, and body fat homeostasis, that affects more than half of U.S. adults 55 years and older. Metsyn is a putative factor for modified host immune response and acceleration of periodontitis. Physical activity and weight loss ameliorate risk of certain Metsyn-related complications, but it is unknown if this extends to periodontal disease. In response to NIDCR PAR-09-182, we propose an extensive secondary data analysis on existing prospective data to examine associations of Metsyn, physical activity and body habitus with measures of prevalence and progression of periodontal disease in a cohort of postmenopausal women. We hypothesize that Metsyn will be associated with higher periodontal disease prevalence and greater progression; that higher physical activity levels and lower body fat levels will modify the association between Metsyn and periodontal disease; and that greater insulin sensitivity and lower systemic inflammatory are, in part, potential mechanisms through which higher physical activity and lower body fat modify the association between Metsyn and periodontitis. The study includes 660 postmenopausal women enrolled in a periodontal disease/osteoporosis study at the Buffalo (NY) center of the Women's Health Initiative. At baseline and at a 5-year reexamination, assessments included standardized oral probing measures and oral radiographs for alveolar crestal height (ACH); dual energy x-ray absorptiometry (DXA) for bone density and body composition; questionnaires on lifestyle habits, oral hygiene and medical history; resting blood pressure; and a fasting blood sample meticulously collected, processed and frozen, that have had relevant biomarkers measured. Our primary dependent variable is based on ACH changes; other periodontal outcomes also will be explored. Metsyn will be defined by National Cholesterol Education Program criteria, using measures of waist girth and/or BMI, blood pressure, and fasting glucose, triglyceride and HDL-C. Concentrations of insulin, and of C-reactive protein and interleukin-6, will be used in defining insulin sensitivity and systemic inflammation, respectively. Strengths are the prospective design and serial standardized oral examinations using calibrated examiners, the well-defined sample of postmenopausal women, DXA measures of body composition, and measured serum biomarkers. This offers advantages over epidemiological studies in which exposures and outcomes are assessed using only questionnaires, blood biomarkers are not available, or the temporal sequence of exposure and outcome assessment is not suitable for etiological hypothesis testing. The extensive database permits examination of confounding and interaction by relevant variables including smoking, medications, and usual dental care. The proposed study aligns with the NIDCR Strategic Plan to integrate molecular, clinical and population work to improve diagnostics and health outcomes. The existing resources for this secondary data analysis provide an unprecedented cost- efficient opportunity to build on established work and expand knowledge in this important area of public health.